The present invention is related to the following co-owned, U.S. patent applications, each of which is hereby incorporated by reference for all purposes: U.S. Ser. No. 60/255,716 filed Dec. 14, 2000 by Safir et al., entitled “Parallel Semicontinuous or Continuous Stirred Reactors”; U.S. Ser. No. 60/209,142 filed Jun. 3, 2000 by Safir et al., entitled “Parallel Semicontinuous or Continuous Stirred Reactors”; U.S. Ser. No. 09/177,170 filed Oct. 22, 1998 by Turner et al., entitled “Parallel Reactor with Internal Sensing and Method of Using Same”, now U.S. Pat. No. 6,548,026, issued Apr. 15, 2003; U.S. Ser. No. 09/211,982 filed Dec. 14, 1998 by Turner et al., entitled “Improved Parallel Reactor with Internal Sensing”, now U.S. Pat. No. 6,306,658, issued Oct. 23, 2001; U.S. Ser. No. 09/548,848 filed Apr. 13, 2000 by Turner et al., entitled “Parallel Reactor with Internal Sensing and Method of Using Same”, now U.S. Pat. No. 6,455,316, issued Sep. 24, 2002; U.S. Ser. No. 09/239,233 filed Jan. 29, 1999 by Wang et al., entitled “Analysis and Control of Parallel Chemical Reactions”, now U.S. Pat. No. 6,489,168, issued Dec. 3, 2002; U.S. Ser. No. 09/205,071 filed Dec. 4, 1998 by Freitag et al., entitled “Continuous Feed Parallel Reactor”, now U.S. Pat. No. 6,485,692, issued Nov. 26, 2002; U.S. Ser. No. 09/174,856 filed Oct. 19, 1998 by Lacy et al., entitled “Graphic Design of Combinatorial Material Libraries”; U.S. Ser. No. 09/420,334 filed Oct. 18, 1999 by Lacy et al., entitled “Graphic Design of Combinatorial Material Libraries”; and U.S. Ser. No. 09/305,830 filed May 5, 1999 by Rust et al., entitled “Synthesizing Combinatorial Libraries of Materials”, now U.S. Pat. No. 6,507,945, issued Jan. 14, 2003.
The aforementioned related applications disclose a number of embodiments for parallel research reactors suitable for use, for example, in combinatorial chemistry applications such as polymer research and catalyst research.
In particular, U.S. application Ser. No. 09/177,170, U.S. Ser. No. 09/211,982, and U.S. Ser. No. 09/548,848 applications disclose a parallel pressure reactor (PPR™) having modular parallel, stirred reactors with temperature and pressure control. U.S. Ser. No. 09/239,233 discloses methodologies and software for controlling such parallel reactors. Although such parallel reactors can be advantageously applied for many polymer research applications (synthesis or screening of materials), the disclosed reactor systems have only limited capabilities for providing multiple reactants to the reaction vessel during the reaction.
Additionally, U.S. Ser. No. 09/205,071 discloses a parallel research reactor that can be adapted for semi-continuous (i.e., semi-batch) or continuous flow operation with one or more feed streams provided to each reactor. Although such a parallel reactor can be advantageously applied for polymer research applications and other research applications requiring semicontinuous or continuous feed, improvements in the disclosed multiple-feed capabilities are desirable, particularly with respect to higher-pressure applications.
Other parallel synthesis reactors are known in the art, particularly in applications directed toward the synthesis of biological polymers (e.g. nucleic acid polymers such as oligonucleotides, or amino acid polymers such as peptides or proteins) or small organic molecules (e.g., having potential pharmaceutical or diagnostic uses), and especially solid-phase synthesis of such compounds. See, for example, U.S. Pat. No. 5,746,982 to Saneii et al., PCT patent application WO 98/13137 of Antonenko et al., European patent application EP 963 791 A2 of Harness et al., PCT patent application WO 97/10896 of Mohan et al., PCT patent application WO 90/02605 of Meldal et al., European patent application EP 658 566 A1 of Chatelain et al., and U.S. Pat. No. 5,792,431 to Moore et al. A system for parallel dissolution testing (e.g., for pharmaceutical compositions) is also known. See, for example, European patent application EP 635 713 A1 of Hutchins et al. These parallel research reactors and other instruments are not, however, generally useful for polymerization research—typically involving higher temperatures, higher pressures and/or in some cases, non-aqueous solvents Moreover, such reactors have limited feed capability during the reaction, and as such, are not generally adaptable for semi-continuous operation with multiple feed streams.
In addition to the aforementioned limitations associated with particular designs, known parallel reactor designs generally suffer from common deficiencies—particularly with respect to applications for polymer research or other applications. In general, known designs are substantially limited with respect to operational flexibility, and do not generally offer higher numbers of feed lines per reactor in combination with desirable higher pressures, higher temperatures, and effective stirring (for polymerization reaction mixtures), in a semicontinuous or continuous operational mode. In particular, the known reactor designs are spatially constrained, and offer limited flexibility for incorporating larger number of feed lines to a relatively small volume reactors. Further, assembly and/or disassembly of the systems (e.g., for reactor vessel access) arc relatively complicated, and would result in significant “down time” during an experimental cycle. Moreover, the known designs do not advantageously provide the desired control of feed addition (e.g. feeding of precise, incremental amounts of reagents) to the reaction vessel during a reaction under reaction conditions. Finally, the known parallel reactors offer only moderate flexibility, if any, with respect to evaluating process/protocol parameter space involving multiple reactants—including the sequence, total volume, rate, and temporal profile of reactant addition to a reaction vessel.